Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial precursor

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Reviewed, UniProtKB/Swiss-Prot P31040 (DHSA_HUMAN)

Last modified June 16, 2009. Version 112. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
    EC=1.3.5.1
Alternative name(s):
    Flavoprotein subunit of complex II
      Short name=Fp

Gene names

Name:	SDHA
Synonyms:	SDH2, SDHF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	664 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Catalytic activity	Succinate + ubiquinone = fumarate + ubiquinol.
Cofactor	FAD.
Pathway	Carbohydrate metabolism; tricarboxylic acid cycle.
Subunit structure	Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Involvement in disease	Defects in SDHA are a cause of complex II mitochondrial respiratory chain deficiency [MIM:252011]; also known as succinate CoQ reductase deficiency. Defects of oxidative phosphorylation give rise to heterogeneous clinical symptoms ranging from isolated organ dysfunction to multisystem disorder. A deficiency of complex II represents a rare cause of mitochondrial encephalomyopathy, leukodystrophy, late-onset optic atrophy and ataxia, myopathy with exercise intolerance, and isolated cardiomyopathy. Defects in SDHA are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions. Ref.3 Ref.6
Miscellaneous	The complex, present in mitochondria, can be degraded to form EC 1.3.99.1, which no longer reacts with ubiquinone.
Sequence similarities	Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.
Sequence caution	The sequence CAA37886.1 differs from that shown. Reason: Miscellaneous discrepancy. Differs extensively from that shown.

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Ontologies

Keywords
Biological process	Electron transport Transport Tricarboxylic acid cycle
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leigh syndrome
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	nervous system development Inferred from mutant phenotype. Source: UniProtKB respiratory electron transport chain Ref.6 Inferred from direct assay. Source: UniProtKB succinate metabolic process Ref.6 Inferred from direct assay. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW tricarboxylic acid cycle Ref.6 Traceable author statement. Source: UniProtKB
Cellular component	mitochondrial respiratory chain complex II Ref.6 Traceable author statement. Source: UniProtKB
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB succinate dehydrogenase (ubiquinone) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 43

Mitochondrion By similarity

Chain

44 – 664

621

Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial

PRO_0000010335

Regions

Nucleotide binding

91 – 106

FAD By similarity

Sites

Active site

340

Proton acceptor By similarity

Binding site

296

Substrate By similarity

Binding site

308

Substrate By similarity

Binding site

407

Substrate By similarity

Binding site

451

Substrate By similarity

Amino acid modifications

Modified residue

Tele-8alpha-FAD histidine By similarity

Modified residue

179

N6-acetyllysine By similarity

Modified residue

252

Phosphothreonine By similarity

Modified residue

485

N6-acetyllysine By similarity

Modified residue

498

N6-acetyllysine By similarity

Modified residue

538

N6-acetyllysine By similarity

Modified residue

547

N6-acetyllysine By similarity

Natural variations

Natural variant

F → V: dbSNP rs1061518.

VAR_049214

Natural variant

D → V: dbSNP rs34635677.

VAR_049215

Natural variant

240

E → Q: dbSNP rs1041946.

VAR_049216

Natural variant

524

A → V in LS. Ref.3

VAR_016878

Natural variant

554

R → W in LS. Ref.6

VAR_002449

Natural variant

555

G → E in complex II deficiency and LS. Ref.9

VAR_016879

Natural variant

657

V → I: dbSNP rs6962. Ref.2

VAR_049217

Experimental info

Sequence conflict

356

G → D in AAD51006. Ref.3

Sequence conflict

398

E → D in AAD51006. Ref.3

Sequence conflict

591

A → T in AAD51006. Ref.3

Sequence conflict

596

D → G in AAD51006. Ref.3

Sequence conflict

600

R → Q in AAD51006. Ref.3

Sequence conflict

629

Y → F in AAA20683. Ref.2

Sequence conflict

640

E → G in AAD51006. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

P31040-1 [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 180B664E3FFD0B34
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FASTA

664

72,692

        10         20         30         40         50         60 
MSGVRGLSRL LSARRLALAK AWPTVLQTGT RGFHFTVDGN KRASAKVSDS ISAQYPVVDH 

        70         80         90        100        110        120 
EFDAVVVGAG GAGLRAAFGL SEAGFNTACV TKLFPTRSHT VAAQGGINAA LGNMEEDNWR 

       130        140        150        160        170        180 
WHFYDTVKGS DWLGDQDAIH YMTEQAPAAV VELENYGMPF SRTEDGKIYQ RAFGGQSLKF 

       190        200        210        220        230        240 
GKGGQAHRCC CVADRTGHSL LHTLYGRSLR YDTSYFVEYF ALDLLMENGE CRGVIALCIE 

       250        260        270        280        290        300 
DGSIHRIRAK NTVVATGGYG RTYFSCTSAH TSTGDGTAMI TRAGLPCQDL EFVQFHPTGI 

       310        320        330        340        350        360 
YGAGCLITEG CRGEGGILIN SQGERFMERY APVAKDLASR DVVSRSMTLE IREGRGCGPE 

       370        380        390        400        410        420 
KDHVYLQLHH LPPEQLATRL PGISETAMIF AGVDVTKEPI PVLPTVHYNM GGIPTNYKGQ 

       430        440        450        460        470        480 
VLRHVNGQDQ IVPGLYACGE AACASVHGAN RLGANSLLDL VVFGRACALS IEESCRPGDK 

       490        500        510        520        530        540 
VPPIKPNAGE ESVMNLDKLR FADGSIRTSE LRLSMQKSMQ NHAAVFRVGS VLQEGCGKIS 

       550        560        570        580        590        600 
KLYGDLKHLK TFDRGMVWNT DLVETLELQN LMLCALQTIY GAEARKESRG AHAREDYKVR 

       610        620        630        640        650        660 
IDEYDYSKPI QGQQKKPFEE HWRKHTLSYV DVGTGKVTLE YRPVIDKTLN EADCATVPPA 


IRSY

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria." Hirawake H., Wang H., Kuramochi T., Kojima S., Kita K. J. Biochem. 116:221-227(1994) [PubMed: 7798181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The cDNA sequence of the flavoprotein subunit of human heart succinate dehydrogenase." Morris A.A.M., Farnsworth L., Ackrell B.A.C., Turnbull D.M., Birch-MacHin M.A. Biochim. Biophys. Acta 1185:125-128(1994) [PubMed: 8142412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-657. Tissue: Heart.
[3]	"Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome." Parfait B., Chretien D., Roetig A., Marsac C., Munnich A., Rustin P. Hum. Genet. 106:236-243(2000) [PubMed: 10746566] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LS VAL-524.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[5]	"Cloning of the flavoprotein subunit of human succinate dehydrogenase." Malcovati M., Marchetti L., Zanelli E., Tenchini M.L. (In) Curti B., Ronchi S., Zanetti G. (eds.); Flavins and flavoproteins 1990, pp.727-730, Walter de Gruyter, Berlin (1991) Cited for: PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[6]	"Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency." Bourgeron T., Rustin P., Chretien D., Birch-MacHin M.A., Bourgeois M., Viegas-Pequignot E., Munnich A., Roetig A. Nat. Genet. 11:144-149(1995) [PubMed: 7550341] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 546-562, VARIANT LS TRP-554.
[7]	"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 76-92 AND 398-418. Tissue: Adipocyte.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II." Van Coster R., Seneca S., Smet J., Van Hecke R., Gerlo E., Devreese B., Van Beeumen J., Leroy J.G., De Meirleir L., Lissens W. Am. J. Med. Genet. A 120:13-18(2003) [PubMed: 12794685] [Abstract] Cited for: VARIANT COMPLEX II DEFICIENCY/LS GLU-555.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases
	D30648 mRNA. Translation: BAA06332.1. L21936 mRNA. Translation: AAA20683.1. AF171030 AF171029 Genomic DNA. Translation: AAD51006.1. BC001380 mRNA. Translation: AAH01380.1. X53943 mRNA. Translation: CAA37886.1. S79641 Genomic DNA. Translation: AAB35332.1.
IPI	IPI00305166.
PIR	JX0336. S21302.
RefSeq	NP_004159.2.
UniGene	Hs.440475
3D structure databases
HSSP	HSSP built from PDB template 1NEK based on UniProtKB P10444.
SMR	P31040. Positions 54-664.
ModBase	Search...
Protein-protein interaction databases
IntAct	P31040. 4 interactions.
PTM databases
PhosphoSite	P31040.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00305166.
Proteomic databases
PeptideAtlas	P31040.
PRIDE	P31040.
Genome annotation databases
Ensembl	ENSG00000073578. Homo sapiens. [Contig view]
GeneID	6389.
KEGG	hsa:6389.
NMPDR	fig\|9606.3.peg.24978.
Organism-specific databases
GeneCards	GC05P000271.
H-InvDB	HIX0004699. HIX0024859.
HGNC	HGNC:10680. SDHA.
MIM	252011. phenotype. 256000. phenotype. 600857. gene.
Orphanet	506. Leigh syndrome. 3208. Succinate CoQ reductase deficiency.
PharmGKB	PA35605.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P31040.
OMA	P31040. TLEFDNL.
Enzyme and pathway databases
BRENDA	1.3.5.1. 247.
Reactome	REACT_6305. Electron Transport Chain.
Gene expression databases
Bgee	P31040.
CleanEx	HS_SDHA.
GermOnline	ENSG00000073578. Homo sapiens.
Family and domain databases
InterPro	IPR003953. FAD_bind2_N. IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR003952. FRD_SDH_FAD_BS. IPR004112. Fum_Rdtase/Succ_DH_flav_C. IPR011281. Succ_DH_flav_su_fwd. IPR014006. Succ_Dhase_frdA_Gneg. [Graphical view]
Pfam	PF00890. FAD_binding_2. 1 hit. PF02910. Succ_DH_flav_C. 1 hit. [Graphical view]
PRINTS	PR00368. FADPNR.
TIGRFAMs	TIGR01816. sdhA_forward. 1 hit. TIGR01812. sdhA_frdA_Gneg. 1 hit.
PROSITE	PS00504. FRD_SDH_FAD_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00139. Succinic acid.
NextBio	24820.
SOURCE	Search...

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Entry information

Entry name

DHSA_HUMAN

Accession

Primary (citable) accession number: P31040
Secondary accession number(s): Q16395, Q9UMY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents